Antiseptic wound dressing

ABSTRACT

The invention relates to an antiseptic material, in particular as a wound dressing, containing a carrier material and at least one antiseptic together with a surfactant, wherein the carrier material is equipped with a cyclodextrin or cyclodextrin derivative that is loaded in the antiseptic or antiseptics.

The invention relates to an antiseptic material, which in particular canalso be used for wound dressings. It contains a carrier material and oneor more antiseptics and a surfactant.

Antiseptically finished materials for the clinical area, especially forwound care, but also for cosmetic and other purposes, are widely knownand in use. Such materials consist as a rule of a carrier material,which is finished with one or more antiseptics. Both textile materialsand non-textile materials, such as polymer films and foams, come intoquestion as carrier material.

Especially in the area of health care and wound management, antisepticsbased on polyamines and biguanides have proved themselves. For example,chlorhexidine, polyethylenimine (Lupasol®), spermine,triethylenetetramine or also polyhexanide (PHMB, poly(hexamethylenebiguanide) hydrochloride) may be mentioned. Chlorhexidine and PHMB inparticular have a considerable antibacterial potential, wherein PHMBgenerally exerts a lower toxicity on human cells.

Particularly in the wound management, but also in the antibacterialfinishing of textiles for health management and other purposes, theproblem exists, however, that the antibacterial effect of the activesubstances is exhausted after relatively short time. Reason for this isthe poor durability of the active substances on the textile materials.In the wound management, it additionally occurs that the activesubstances are diluted by the wound exudate and are removed (aspirated)together with the wound exudate. This makes a frequent change of thewound dressing necessary, which is not entirely conducive to the woundhealing.

A particular problem exists in wounds that are filled with an absorbentmaterial, closed and subjected to vacuum by means of a pump or suctionbottle. It has been shown that a slight vacuum promotes the healingprocess. An impregnation of the absorbent material with an antisepticwould be advantageous here, but quite generally this is sucked out ofthe wound together with the exudate within entirely short time. As theconsequence, the wound threatens to become infected unless a change ofdressing is carried out regularly. However, a change of dressing isdetrimental to the healing process. A prolongation of the usefullife/duration of action of the antiseptic finish of the wound dressingwould be very desirable here.

Finally, an antiseptic finish of textiles for the health care or theinfection protection, in which the finish remains active over longertime, would also be desirable.

In this context the task of the invention is the provision of anantiseptic material which retains its effectiveness over longer time butsimultaneously acts less toxically on human and animal cells, is simpleto manufacture and simple to handle.

This task is accomplished with an antiseptic material of the typementioned initially, in which the carrier material is finished with acyclodextrin or cyclodextrin derivative, which is loaded with theantiseptic or with several antiseptics.

According to the invention, any material that is finished antisepticallyin the described way is understood as antiseptic material. Such amaterial respectively has a carrier material, which contains anantiseptic and a surfactant. Textile materials in particular come intoquestion as carrier material, wherein they may be woven textile fabricsor nonwovens. Plastics also come into question as carrier material,especially porous plastic foams, as find application in the medicine inthe wound treatment, especially open-porous polyurethanes, which qualifyas eminently body-friendly.

The term “textile materials” includes all types and forms of natural andsynthetic fibers and textiles produced from them. Woven and nonwovenfabrics of cotton and polyester can be mentioned in particular.

Polyamines and biguanides in particular come into question asantiseptics, wherein the term “polyamine” includes both antisepticallyacting multifunctional amines and also polymeric amines. Biguanides,including chlorhexidine and polyhexanide, are preferred.

The carrier materials used according to the invention are finished witha cyclodextrin or cyclodextrin derivative. The known α-, ρ- andγ-cyclodextrin forms are understood as cyclodextrins, wherein they arecyclic sugar molecules with 6, 7 or 8 α-D-glucose units. Thesecyclodextrins may be derivatized in the usual way. Furthermore, they maybe provided with anchor groups known in and for themselves, via which abinding to a carrier material takes place. This binding may take placein chemical way, in physical way via interactions or else purelymechanically via so-called anchor groups, which interlock with thecarrier material. A physical binding takes place, for example, viaelectrostatic interactions or via chemical interactions between themolecule or its derivative, for example hydrophilic/hydrophobicinteractions of the cyclodextrin with the surroundings and the surfaceof the carrier material. All of these methods are adequately describedin the literature.

By cyclodextrin derivatives, derivatives of the α-, β- andγ-cyclodextrins are known that in addition to an anchor group have afurther functionalization in order to achieve desired effects. Suchderivatives are to be selected such that they exert not any negative butif necessary a positive influence on the complex formation of thecyclodextrin with the antiseptic.

Common surfactants come into question as surfactants, but especiallybetaines. Especially undecylenic amidopropyl betaine andtrimethylammonium acetate would have to be mentioned here. As a rule thesurfactants are bound not to the cyclodextrin but instead viaelectrostatic interactions to the carrier material.

The carrier material coming into use according to the invention as arule contains 1 to 5 wt % cyclodextrin or derivative thereof, especially3 wt %, relative to the weight of the carrier material. Investigationshave shown that, with proper process control, almost all cyclodextrinunits are loaded in the usual case with one molecule of the antiseptic,i.e. the ratio of the cyclodextrin molecules to the molecules of theantiseptic lies in the range of 0.1 to 1.0. Where the surfactant orbetaine is concerned, as a rule it is contained in the antisepticmaterial approximately in the same amount as the antiseptic.

Investigations have shown that the antiseptic material according to theinvention has a high bactericidal activity and in addition isantivirally and fungicidally active. The fungicidal activity is obtainedabove all by the addition of the betaine, which is capable of detachingbiofilms from wound surfaces and of promoting the penetration of theantiseptic into the wound. It exerts a kind of entrainment effect. Testswith pathogenic germs, especially of S. aureus, E. coli and C. albicans,have achieved a practically 100% inhibition of the microorganism in ashort time.

In addition, cyclodextrins are suitable for assimilating proteinsubstances and other decomposition products of body cells and ofremoving them from the surroundings. A healing-promoting andsimultaneously also odor-reducing effect is derived from this. The woundis kept cleaner on the whole. Associated with the assimilation of suchdecomposition products is the release of antiseptics, which arecontained in the cyclodextrin and which in this way are deliveredgradually into the wound region. This is responsible for the lastingeffect of the antiseptic materials according to the invention.

The antiseptic materials according to the invention may be used for amultiplicity of purposes. This is especially the use in conjunction withthe wound care as wound dressing, bandage material or plasters. Foamsmay be used for the filling of wounds in the course of a vacuum therapy.Furthermore, in the clinical area, everyday textiles for health care,such as bed linens, gowns, patient clothing and the like, may befinished accordingly. A further application is that in cosmetic patches,and also for work garments outside hospitals in areas in whichcontamination with microorganisms cannot be ruled out. Finally, such afinish may also be used for the surface treatment of garments that areused for the protection of the transmission of bacteria and viruses and,for example, is specified for Mecca pilgrims. Everyday textiles may bereloaded after the laundering.

Particularly preferred antiseptic materials have a carrier material thatis finished with β-cyclodextrin that is loaded with polyhexanide.Undecylenic amidopropyl betaine is present as the betaine. Thiscyclodextrin is bound via an anchor group to a polysaccharide, whichwill be applied onto the carrier material. In particular, commongel-forming polysaccharides come into question as the polysaccharide,such as carrageenan, tragacanth, guar, fucoidan or alginate. The bindingof the cyclodextrin takes place by reaction ofmonochlorotriazenyl-β-cyclodextrin in water at an elevated temperature(90° C.) in the presence of sodium hydroxide solution at a pH of 11 to12. The product so obtained, in which the β-cyclodextrin is bound to thepolysaccharide, may be applied durably onto the carrier material byspraying or padding. It remains there even after several launderings.

The loading of the cyclodextrin with the antiseptic takes place byimmersing the carrier material in a solution of the antiseptic, byspraying the antiseptic or by reacting themonochlorotriazenyl-β-cyclodextrin with the polysaccharide in thepresence of the antiseptic manufactured. In the latter case, it must beensured that undesired side reactions do not occur.

A further preferred form of the binding of the cyclodextrin to thecarrier material may be achieved via polyvinylamine or polyethylenimine.β-Cyclodextrin-substituted polyvinylamine or polyethylenimine adheresexcellently to the surface of textiles, but also of polyurethane foams,which is why correspondingly finished carrier material is also suitablein particular for wound treatment, but also for garments.

Accordingly, the invention also relates to an aqueous solution, whichcontains a cyclodextrin bound to a polyvinylamine or polyethylenimine,which is loaded with polyhexamide and additionally contains undecylenicamidopropyl betaine.

Tests have shown that a carrier material that is finished with 3%polyvinylamine-β-cyclodextrin and is loaded with approximately equalamounts of PHMB and undecylenic amidopropyl betaine, hereinafterreferred to as the PHMB/betaine complex or complex, has a series ofadvantageous properties:

-   -   The PHMB/betaine complex has cationic properties and binds        excellently to OH bonds, such as are present in cellulose, for        example. An aqueous solution of the correspondingly loaded        polyvinylamine-β-cyclodextrin complex may be used appropriately        for decontamination and prevention of infection.    -   The complex exhibits a very good biocompatibility index with a        high “killing rate” for microorganisms and a low toxicity toward        human cells (tested on HaCaT cells). An accelerated wound        healing and a very low infection rate have been shown.    -   The complex is capable of stabilizing the pH environment of a        wound at 5.5 and thus of creating prerequisites for the wound        conditioning. In chronic wounds, the pH is regularly in the        alkaline range. At pH 5.5, the wound healing proceeds much        faster.    -   The combination of PHMB and betaine dissolves biofilms and thus        cleans the wound. It creates an optimal wound environment for        faster regeneration of granulation tissue.    -   The complex durably inhibits free radicals, which are capable of        damaging cells.    -   The complex is capable of absorbing exudate, especially        proteins, from the wound and neutralizing it. In this way        microorganisms are deprived of the nutritional basis.

EXAMPLES

The invention will be described in more detail by the followingexamples.

The solutions prepared in the following examples are suitable for thespraying of textile materials, foams, etc. of the most diversematerials, such as, for example, polyester, cotton, polyacrylonitrile,glass fibers, polyurethane, etc. The fixation of the cyclodextrinderivatives takes place by electrostatic and hydrophobic interactionswith the respective surface.

It is not permissible to exceed the cited concentrations substantially,since otherwise intensive gel formation sets in and reaction solutioncan no longer be sprayed onto textile materials.

Example 1 Reaction with Carrageenan (Fluka)

1 g Carrageenan is dissolved together with 2 gmonochlorotriazenyl-β-cyclodextrin (Wacker) in 200 water. The solutionis heated to 90° C. and a solution of sodium hydroxide (15 g/L) isslowly added dropwise until a pH of 11 to 12 is established. After onehour, the solution is cooled and neutralized with hydrochloric acid.

Corresponding cyclodextrin derivatives were prepared with the followingpolysaccharides:

Tragacanth (Merck) Guar (Sigma) Fucoidan (Sigma) Carrageenan/Fucoidan

The cyclodextrin derivatives synthesized in this example do not have anykind of biostatic effects. The biostatic action of the finish can bedetermined by means of the formazan test (F. P. Altman, Progr.Histochem. Cytochem. 9 (1976); W. Oppermann, R. Gutmann, S. Schmitt, E.Held-Föhn, Textilveredelung 37, 19 (2003)).

Example 2

In order to prepare cyclodextrin derivatives with bothprotein-adsorptive and biostatic properties, the following cyclodextrinderivatives were synthesized.

Reaction with Guar and Triethylenetetramine (Fluka)

1 g guar is dissolved together with two 2 gmonochlorotriazenyl-β-cyclodextrin in 200 mL water. The solution isheated to 90° C. and a solution of triethylenetetramine (1 g/L) isslowly added dropwise until a pH of 11 to 12 is established. After onehour, the solution is cooled and neutralized with hydrochloric acid.

After the spraying of the solution onto a woven polyester fabric, thisis dried at room temperature. An inhibition of the growth of 80% ismeasured by means of the formazan test.

Correspondingly, further protein-adsorptive cyclodextrin derivativeswith biostatic properties were prepared:

Water-soluble starch/polyethylenimine (Lupasol®, BASF), inhibition 53%Tragacanth/triethylenetetramine, inhibition 82%Carrageenan/triethylenetetramine, inhibition 0%Carrageenan/spermine (Fluka), inhibition 10%Guar/diethylenetriamine (Fluka), inhibition 20%Guar/1,2-diaminopropane (Fluka), inhibition 34%

Example 3 Examples of the Finishing of Textile Materials

A) The solutions prepared in Examples 1 and 2 are sprayed onto a wovenfabric of cotton and dried at elevated temperature (40 to 80° C.). Thecyclodextrins on the woven fabric surface can be detected in each sampleby means of a basic phenolphthalein solution. If one drop of this violetsolution is placed on the woven cotton fabric, then a decolorizationtakes place due to the complex formation between the cyclodextrin andthe phenolphthalein.

For the detection of the protein binding, commercial protein powder isused. After an immersion in the protein solution, for several minutes,of the samples, which had been sprayed with the solutions prepared inExamples 1 and 2 and dried, the textile is carefully rinsed off withdistilled water. Thereafter the textile samples are immersed in diluteaqueous sodium hydroxide solution and a couple of drops of coppersulfate solution are added. A staining of the samples is observed, whichmay be attributed to the presence of proteins.

B) The solutions prepared in Examples 1 and 2 are sprayed onto a wovenfabric of polyester and dried. The detection of the presence ofcyclodextrin and the binding of protein powder were performedcorrespondingly and yielded analogous results.

C) Instead of woven fabrics of cotton and polyester, woven fabrics ofpolyacrylonitrile, other synthetic and regenerative fibrous materials,foams of polyurethanes and the like are also suitable. The procedurecorresponds to that described under A), the results correspond to theresults obtained there.

Example 4 Cyclodextrin Derivatives with Reactive Anchor Groups

Suitable cyclodextrin derivatives are described in the correspondingpatent literature. The preparation of monochlorotriazine-substitutedβ-cyclodextrin is known from DE 44 29 229 and of further cyclodextrinderivatives with one or more reactive anchor groups from DE 101 55 781.

A binding of cyclodextrin to fibrous materials is also possible by theuse of bifunctional or polyfunctional reagents, such as viadiisocyanates and the like (W. Volz, Anti-Smell Finishes in TextileProcessing, Textilveredelung 38, 17 (2003)), or by the use ofdimethylureas and similar compounds, such as are also used forcrease-resistant finishing of cellulosic materials (H.-J. Burschmann, D.Knittel, E. Schollmeyer: Crease-resistant finishing of cotton in thepresence of cyclodextrins for incorporation of fragrances, MelliandTextilbiler. 72, 198 (1991)).

Example 5 Finishing of Textile Materials with Cyclodextrin andAntiseptics

Especially chlorhexidine and polyhexanide in aqueous solution are usedas antiseptics.

Three finishing variants with cyclodextrin derivatives, which are boundto the textile by ionic or hydrophobic interactions, are presented:

A) The textile material or the foam is finished with cyclodextrins. Forthis purpose, an aqueous solution of a cyclodextrin derivative (seeabove) or an aqueous solution of a cyclodextrin substituted withpolyvinylamine or polyethylenimine (approx. 3% cyclodextrin content) issprayed onto the material to be finished. An aqueous solution of theantiseptic (0.08 to 0.22% PHMB; 0.1 to 0.15% betaine) is sprayedsimultaneously, wherein both solutions must have a pH of 5 to 7, sinceotherwise the formation of a precipitate takes place.

B) The textile material or the foam is finished with cyclodextrins. Forthis purpose, an aqueous solution of a cyclodextrin derivative (seeabove) or an aqueous solution of a cyclodextrin substituted withpolyvinylamine or polyethylenimine (approx. 3% cyclodextrin content)with a pH of 5 to 7 is sprayed onto the material to be finished anddried. Then an aqueous solution of the antiseptic (0.1% PHMB; 0.1%betaine) is sprayed. The application of both solutions may also beperformed by means of a padding machine.

C) A mixture of the cyclodextrin derivative (see above) or of acyclodextrin substituted with polyvinylamine or polyethylenimine and ofthe antiseptic is prepared in aqueous solution by mixing both components(equimolar, preferably 0.001 to 0.01 mol/L), wherein the aqueous phasemust have a pH of 5 to 7, in order to prevent the formation of aninsoluble precipitate. The resulting aqueous solution is sprayed ontothe textile material or is applied onto the textile material or the foamby an application by means of a padding machine.

Example 6 Finishing Variant with a Cyclodextrin Derivative with aReactive Group

A woven cotton fabric is immersed in an aqueous solution ofmonochlorotriazinyl-β-cyclodextrin (sodium salt, 20-100 g/L) (Cavasol®W7 MCT, Wacker-Chemie GmbH), which has been adjusted to a pH of 4 to 6with acetic acid (60%). Then the fabric is quetched on a padding machine(liquor uptake approx. 70%). Thereafter the fabric is predried at 80° C.for 10 minutes and then fixed at 160° C. for 7 minutes. Then an aqueoussolution of the antiseptic (0.1% PHMB) is sprayed on or applied by anapplication by means of a padding machine. At the same time orsubsequently, the betaine is applied from aqueous solution (0.1%betaine).

The FIGURE schematically shows a cyclodextrin molecule with polyhexamideloading and an anchor group, which mechanically anchors the cyclodextrinonto a textile fiber.

1. Antiseptic material, especially wound dressing, containing a carriermaterial and at least one antiseptic together with a surfactant, whereinthe carrier material is finished with a cyclodextrin or cyclodextrinderivative, which is loaded with the antiseptic.
 2. Antiseptic materialaccording to claim 1, wherein the carrier material is a polymeric foam,especially a porous polyurethane foam.
 3. Antiseptic material accordingto claim 1, wherein the carrier material is a textile carrier material,especially a polyester or cotton.
 4. Antiseptic material according toclaim 1, wherein the carrier material is finished with a β-cyclodextrinor a β-cyclodextrin derivative.
 5. Antiseptic material according toclaim 1, wherein the cyclodextrin or cyclodextrin derivative is bound tothe carrier material via an anchor group chemically and/or mechanicallyand/or by physical interactions.
 6. Antiseptic material according toclaim 1, wherein the cyclodextrin or cyclodextrin derivative is boundchemically to a polysaccharide, a polyvinylamine or a polyethylenimine,which for its part is bound to the carrier material via physicalinteractions.
 7. Antiseptic material according to claim 1, comprising acontent of 1 to 5 wt % of cyclodextrin or cyclodextrin derivative,relative to the weight of the carrier material.
 8. Antiseptic materialaccording to claim 1, wherein the antiseptic is one from the group ofpolyamines or biguanides.
 9. Antiseptic material according to claim 8,wherein the cyclodextrin or cyclodextrin derivative is loaded withchlorhexidine or polyhexanide.
 10. Antiseptic material according toclaim 1, wherein the molecular ratio of cyclodextrin or cyclodextrinderivative to antiseptic lies in the range of 0.1 to 1.0.
 11. Antisepticmaterial according to claim 1, wherein it contains a betaine. 12.Antiseptic material according to claim 11, wherein the betaine isundecylenic amidopropyl betaine or trimethylammonium acetate. 13.Antiseptic material according to claim 11, wherein it containsantiseptic and betaine in approximately equimolar amounts. 14.Antiseptic material according to claim 1 as wound dressing or plaster.15. Antiseptic material according to claim 1 as everyday textile for thehealth care.
 16. Antiseptic material according to claim 1 as anantimicrobial functional patch for the cosmetics.
 17. Antisepticmaterial according to claim 1 as protective garments finished withbiocide.
 18. Use of a polyvinylamine-β-cyclodextrin with polyhexanideloading in aqueous solution together with a betaine for the preparationof antiseptically finished materials.